Hoffman A L, Makowka L, Banner B, Cai X, Cramer D V, Pascualone A, Todo S, Starzl T E
Department of Surgery, University of Pittsburgh Health Center, Pennsylvania.
Transplantation. 1990 Mar;49(3):483-90. doi: 10.1097/00007890-199003000-00001.
Small intestine allotransplantation in humans is not yet feasible due to the failure of the current methods of immunosuppression. FK-506, a powerful new immunosuppressive agent that is synergistic with cyclosporine, allows long-term survival of recipients of cardiac, renal, and hepatic allografts. This study compares the effects of FK-506 and cyclosporine on host survival, graft rejection, and graft-versus-host-disease in a rat small intestine transplantation model. Transplants between strongly histoincompatible ACI and Lewis (LEW) strain rats, and their F1 progeny are performed so that graft rejection alone is genetically permitted (F1----LEW) or GVHD alone permitted (LEW----F1) or that both immunologic processes are allowed to occur simultaneously (ACI----LEW). Specific doses of FK-506 result in prolonged graft and host survival in all genetic combinations tested. Furthermore, graft rejection is prevented (ACI----LEW model) or inhibited (rejection only model) and lethal acute GVHD is eliminated. Even at very high doses, cyclosporine did not prevent graft rejection or lethal GVHD, nor did it allow long-term survival of the intestinal graft or the host. Animals receiving low doses of cyclosporine have outcomes similar to the untreated control groups. No toxicity specific to FK-506 is noted, but earlier studies by other investigators suggest otherwise.
由于目前免疫抑制方法的不足，人类小肠同种异体移植尚不可行。FK-506是一种强大的新型免疫抑制剂，与环孢素具有协同作用，可使心脏、肾脏和肝脏同种异体移植受者长期存活。本研究在大鼠小肠移植模型中比较了FK-506和环孢素对宿主存活、移植物排斥及移植物抗宿主病的影响。在组织相容性差异很大的ACI和Lewis（LEW）品系大鼠及其F1代之间进行移植，以便单独发生移植物排斥（F1→LEW）或单独发生移植物抗宿主病（LEW→F1），或使两种免疫过程同时发生（ACI→LEW）。特定剂量的FK-506可使所有测试的基因组合中的移植物和宿主存活期延长。此外，可预防移植物排斥（ACI→LEW模型）或抑制移植物排斥（仅排斥模型），并消除致死性急性移植物抗宿主病。即使使用非常高的剂量，环孢素也不能预防移植物排斥或致死性移植物抗宿主病，也不能使肠道移植物或宿主长期存活。接受低剂量环孢素的动物的结果与未治疗的对照组相似。未观察到FK-506特有的毒性，但其他研究者早期的研究结果则相反。
